Two phase 1 drug interaction studies performed in healthy volunteers.

24/12/2015 - A parallel-treatment design (n = 41) was used to evaluate the effects of itraconazole (200 mg once daily) on the pharmacokinetics of enzalutamide and its active metabolite N-desmethyl enzalutamide after a single dose of enzalutamide (160 mg). Coadministration of itraconazole increased the composite AUC(0-inf) by 1.3-fold. A single-sequence crossover design (n = 14) was used to determine the effects of enzalutamide 160 mg/day on the pharmacokinetics of a single oral dose of sensitive substrates for CYP2C8 (pioglitazone 30 mg), CYP2C9 (warfarin 10 mg), CYP2C19 (omeprazole 20 mg), or CYP3A4 (midazolam 2 mg). Enzalutamide reduced the AUC(0-inf) of oral S-warfarin, omeprazole, and midazolam by 56, 70, and 86 %, respectively; therefore, enzalutamide is a moderate inducer of CYP2C9 and CYP2C19 and a strong inducer of CYP3A4. The authors recommended to avoid concomitant use of enzalutamide with narrow therapeutic index drugs metabolized by CYP2C9, CYP2C19, or CYP3A4, as enzalutamide may decrease their exposure.

Pharmacokinetic Drug Interaction Studies with Enzalutamide.

Jacqueline A. Gibbons, Michiel de Vries, Walter Krauwinkel, Yoshiaki Ohtsu, Jan Noukens, Jan-Stefan van der Walt, Roelof Mol, Joyce Mordenti, Taoufik Ouatas

Clin Pharmacokinet (2015) 54:1057–1069

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